Matthew R. Hodges , Ph.D.
Phone: (414) 955-7528
B.A. Biology, Carleton College, 1998
Ph.D. Physiology, Medical College of Wisconsin, 2004
Parker B. Francis Fellow, Yale University School of Medicine, 2006-2009
Every cell in the body requires a continuous supply of oxygen and constant removal of carbon dioxide, and as a result we breathe continuously from birth to death to ensure adequate gas exchange. A decrease in the blood oxygen levels or an increase in carbon dioxide (which decreases pH) both acting to increase ventilation in classic feedback fashion. However, it remains unknown which neurons within the brainstem serve as detectors of brain carbon dioxide (CO2) levels and/or pH, and how these neurons send this information to the neuronal network that generate respiratory rhythm and muscle activation patterns.
We are currently using fluorescence-activated cell sorting (FACS) of primary neurons to collect CO2-activated serotonergic (5-HT) and glutamatergic (RTN) neurons and compare them to cells that are not activated by high CO2 and/or low pH. We extract mRNAs from these cell pools and identify and measure the expression levels of all genes in order to determine which genes are uniquely expressed in the CO2-sensitive populations. These gene targets are then manipulated in vitro (neuronal recordings and pharmacologic agents) or in vivo (knockout or mutant rat strains) to verify their potential role in breathing control and pH homeostasis. This project is funded by the NIH.
Sudden Infant Death Syndrome (SIDS) is a leading cause of post-neonatal mortality in the U.S. and the Western World. SIDS is a devastating disease, and one that is difficult to understand. Recent research has identified abnormalities in the brainstem serotonin (5-HT) system in SIDS cases, suggesting the neurons that make 5-HT could contribute to the sudden and unexpected death. In the Hodges Lab, we study the effects of brain depletion of tryptophan hydroxylase, and as a result brain depletion of 5-HT. We study how these abnormalities, which are found in SIDS, affect physiological systems necessary for sustaining life, like breathing and body temperature control, and how additional environmental (increased heat) and other (inflammation) stressors affect these systems. This project is a collaboration with the PI (Hodges) and Drs. Cummings (University of Missouri) and Huxtable (University of Oregon), and was previously funded by the NIH and Children’s Research Institute at CHW (additional funding pending).
We are also currently studying the role of a potassium ion channel subunit gene (Kcnj16) and how it contributes to the acute and chronic regulation of body pH. We are gaining major insights into the role of Kcnj16 in the control of breathing and the CO2 chemoreflex by studying rats with a truncation mutation in the coding region of the gene. These rats may be important rodent models for the epilepsy and potentially Sudden Unexplained Death in Epilepsy (SUDEP). This project is collaboration with the PI (Hodges) and Dr. Oleg Palygin (Physiology). This project is funded by the Advancing Healthier Wisconsin Foundation and Neuroscience Research Center at MCW.
A fourth project ongoing in the lab is the study of changes in ventilatory control associated with neonatal lung dysfunction, using a rodent model of bronchopulmonary dysplasia. While the lungs are the primary cause of ventilatory distress in babies with pulmonary disease, ultimately the neural network that controls breathing that adapts to this abnormality and adapts. The extent of this neural adaptation, or neuroplasticity is unclear, but has become another focus of research in the lab. This project is a collaboration with the PI (Hodges) and two additional MCW faculty, Drs. Konduri (Section Chief, Neonatology) and Wong-Riley (Professor, Cell Biology, Neurobiology and Anatomy), and is funded by the Children’s Research Institute at CHW.
In addition to training 8 undergraduate and 2 medical students in the Hodges Lab, graduate students from the Physiology Doctoral Program and Neuroscience Doctoral Programs have obtained their PhD in the lab, including:
Gary C. Mouradian, Jr., PhD – Currently a Post-doctoral Fellow at the University of Colorado-Denver, Anschutz Medical Campus, Denver, CO
Madeleine M. Puissant, PhD – Currently an EMS Faculty and Clinical Coordinator, Northcentral Technical College, Wausau, WI
Recent and Representative Publications (46 total):
- M.M. Puissant, A.E. Echert, C. Yang, G.C. Mouradian Jr., T. Novotny, P. Liu, M. Liang, M.R. Hodges. RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2-insensitive Brown Norway rat. J. Physiol. 593(2):415-430, 2015. PMID: 25384776.
- L. Li, Y. Lu, E. Chen, C. Yang, P. Jayaraman, J. De Pons, C.C. Kaczorowski, H.J. Jacob, A.G. Greene, M.R. Hodges, A.W. Cowley, Jr., M. Liang, H. Xu, P. Liu. Improved rat genome gene prediction by integration of ESTs with RNA-Seq information. Bioinformatics 31(1):25-32, 2015. PMID:25217576.
- C. Muere, S. Neumueller, J. Miller, S. Olesiak, M.R. Hodges, L. Pan, and H.V. Forster. Evidence for neuromodulator interdependence in the control of breathing after cholinergic disruption in the ventral respiratory column during wakefulness and NREM sleep. Respir. Physiol. Neurobiol. PMID:25262584.
- P.F. Martino, S. Olesiak, D. Batuuka, D. Riley, S. Neumueller, H.V. Forster, M.R. Hodges. Strain differences in pH-sensitive K+ channel-expressing cells in chemosensory and non-chemosensory brainstem nuclei. J. Appl. Physiol. 117(8):848-56, 2014. PMID:25150225.
- M.R. Hodges, A.E. Echert, M.M. Puissant, and G.C. Mouradian. Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats. Respir. Physiol. Neurobiol. 186(2):221-228, 2013. PMID: 23454023.
- K. Katter, A.M. Geurts, O. Hoffmann, L. Mates, V. Landa, L. Hiripi, C. Moreno, J. Lazar, S. Bashir, V. Zidek, E. Popova, B. Jerchow, K. Becker, A. Devaraj, I. Walter, M. Grzybowski, M. Corebett, A.R. Filho, M.R. Hodges, M. Bader, Z. Ivics, H.J. Jacob, M. Pravenec, Z. Bosze, T. Rulicke, Z. Izsvak. Transposon-mediated transgenesis, transgenic rescue, and tissue-specific gene expression in rodents and rabbit. FASEB J. 27(3):930-941, 2013. PMID: 23195032.
- M.R. Hodges, S. Best, G.B. Richerson. Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice. Respir. Physiol. Neurobiol. 177(2): 133-40, 2011. PMID:21453797.
- M.R. Hodges, M. Wehner, J. Aungst, J.C. Smith, G.B. Richerson. Transgenic mice lacking serotonin neurons have severe apnea and high mortality during development. J. Neurosci. 29(33): 10341-9, 2009. PMID:19692608.
- M.R. Hodges, G.B. Richerson. Interaction between defects in ventilatory and thermoregulatory control in mice lacking 5-HT neurons. Respir. Physiol. Neurobiol. 164(3): 350-357, 2008. PMID:18775520.
- M.R. Hodges, G.J. Tattersall, M.B. Harris, S. McEvoy, D. Richerson, E.S. Deneris, R.L. Johnson, Z.F. Chen, G.B. Richerson. Defects in the breathing and thermoregulation in mice with near-complete absence of central serotonin neurons. J. Neurosci. 28 (10): 2495-2505, 2008. PMID:18322094.
Title: Molecular mechanisms of central CO2 chemoreception
Source: NIH R01 HL122358
Role: Principal Investigator
PI: Dr. Matthew R. Hodges
Dates: 4/17/2015 – 3/31/2020
Direct Funds: $1,250,000 (total for 5 years)
Title: Interdependence among neuromodulators of ventilatory control
Source: NIH R01 HL112996
PI: Dr. Hubert V. Forster
Dates: 8/1/2013 – 4/30/2017
Direct Funds: $984,000 (total for 4 years)
Title: Kir channels in epilepsy and ventilatory control
Source: Advancing a Healthier Wisconsin
Role: Co-principal Investigator
PIs: Drs. Matthew R. Hodges and Oleg Palygin
Dates: 1/1/2015 – 12/30/2016
Direct Funds: $50,000 (total for 2 years)
Title: Altered chemoreceptor signaling after neonatal lung injury and risk of SIDS
Source: Children’s Hospital of Wisconsin Research Institute
PIs: Dr. Ganesh Konduri
Dates: 1/1/2016 – 12/30/2019
Direct Funds: $640,000 (total for 3 years)